Dideoxycytidine (ddC) and dideoxyadenosine are undergoing trials in patients with AIDS. Studies on the metabolism of these and allied dideoxynucleosides in human cells have continued. Although dideoxycytidine undergoes a metabolic fate which is principally anabolic, the half-life of its most important anabolite, the 5'- triphosphate, is comparatively brief, approximating 6 hours in Molt-4 and CEM lymphoblasts. By contrast, the metabolic fate of ddA is principally catabolic, but its 5'-triphosphate decays with a t 1/2 well in excess of 24 hours. Two potentially important metabolites of these agents have been identified. In addition to the phosphate esters and diesters reported previously, we have found that ddC is also converted to a molecule with all the properties of dideoxycytidine diphosphoethanolamine. Dideoxyadenosine, after deamination, is phosphorylyzed to yield hypoxanthine and the extremely labile dideoxy sugar, dideoxyribose- 1-phosphate. Since it has been shown that this transitory catabolite can be utilized by other nucleoside phosphorylases (acting in the preferred, synthetic direction), the operation of this reaction offers the potential of allowing the interconversion of a comparatively inert agent (such as dideoxythymidine EC50: 100 micromolar to a potent species such as ddI (EC50: 5 micromolar) or vice versa.